Publication: Sıçanlarda diyabetle indüklenen alzheimer modelinde Sodyum-Glukoz Ko-Transporter inhibitörlerinin etkilerinin incelenmesi
Abstract
1. ÖZET Tezin Başlığı : Sıcanlarda Diyabetle İnduklenen Alzheimer Modelinde Sodyum- Glukoz Ko-Transporter İnhibitorlerinin Etkilerinin İncelenmesi Oğrencinin Adı, Soyadı : Ayşe Nur Yavuz Danışmanın Adı, Soyadı : Prof. Dr. Levent Kabasakal Programın Adı : Farmakoloji Amac: Bu tez calışmasında T2DM ile induklenen AH modelinde non-selektif sodyum-glukoz ko-transporter (SGLT) inhibitoru florizin ile SGLT2 inhibitoru dapagliflozinin etkileri ve etki mekanizmalarının aydınlatılması amaclanmıştır. Gerec ve Yontem: Calışmamızda 8 hafta yuksek yağlı diyet ile beslenme ve 4. haftanın sonunda duşuk doz streptozotosin uygulaması ile diyabet induklu AH modeli oluşturulmuştur. Streptozotosin uygulamasının ardından 4 haftalık tedavi başlanmıştır. Deney suresince sıcanların hiperglisemi durumları, kan glukoz olcumu, oral glukoz tolerans testi ve insulin tolerans testi ile; kognitif bozuklukları ise yeni obje tanıma testi, pasif sakınma testi ve Morris’in su tankı testi ile değerlendirilmiştir. Sıcanlardan elde edilen serum ve ceşitli dokularda ilgili parametrelerin biyokimyasal ve histolojik analizleri yapılmıştır. Bulgular: Florizin ve dapagliflozin, diyabetik ve kognitif bozuklukları duzeltmiş ve biyokimyasal analizler bu sonucları desteklemiştir. Histolojik analize gore pankreas, hipokampus ve serebral korteks dokularında AH grubuna gore duzelme saptanmış, immunohistokimyasal analizlerde hipokampus ve serebral kortekste AH grubunda artan amiloid-b1-42 ve tau protein ekspresyonu azalmıştır. Sonuclar: Bu tez calışmasından elde edilen sonuclara gore non-selektif SGLT inhibitoru florizin ve SGLT2 inhibitoru dapagliflozin T2DM induklu AH hastalığında iyileştirici etki gostermiştir.
2. SUMMARY Title of Thesis : Investigation of the Effects of Sodium-Glucose Co-Transporter Inhibitors in Diabetes-Induced Alzheimer Model in Rats Student Name, Surname : Ayşe Nur Yavuz Supervisor Name : Prof. Dr. Levent Kabasakal Program Name : Farmakoloji Objective: In this thesis, it was aimed to elucidate the action and mechanism of action of the non-selective sodium-glucose co-transporter (SGLT) inhibitor phlorizin and the SGLT2 inhibitor dapagliflozin in the T2DM-induced AD model. Material and Methods: In our study, the T2DM-induced AH model was created with high-fat diet for 8 weeks and low-dose streptozotocin administration at the end of the 4th week. After streptozotocin administration, 4-week treatment was started. During the experiment, the hyperglycemia status of rats were evaluated with blood glucose measurement, oral glucose tolerance test, and insulin tolerance test; cognitive impairments were evaluated with the novel object recognition test, passive avoidance test and Morris' water maze test. Biochemical and histological analyzes of the relevant parameters were performed in serum and tissues obtained from rats. Results: Phlorizin and dapagliflozin improved diabetic and cognitive impairments, and biochemical analyzes supported these results. According to the histological analysis, pancreatic, hippocampus and cerebral cortex tissues showed improvement compared to the AD group, and immunohistochemical analyzes showed increased amyloid-b1-42 and and tau protein expression in the hippocampus and cerebral cortex in the AD group. Conclusion: According to the results obtained from this thesis study, non-selective SGLT inhibitor florizin and SGLT2 inhibitor dapagliflozin showed curative effects in T2DM-induced AD disease.
2. SUMMARY Title of Thesis : Investigation of the Effects of Sodium-Glucose Co-Transporter Inhibitors in Diabetes-Induced Alzheimer Model in Rats Student Name, Surname : Ayşe Nur Yavuz Supervisor Name : Prof. Dr. Levent Kabasakal Program Name : Farmakoloji Objective: In this thesis, it was aimed to elucidate the action and mechanism of action of the non-selective sodium-glucose co-transporter (SGLT) inhibitor phlorizin and the SGLT2 inhibitor dapagliflozin in the T2DM-induced AD model. Material and Methods: In our study, the T2DM-induced AH model was created with high-fat diet for 8 weeks and low-dose streptozotocin administration at the end of the 4th week. After streptozotocin administration, 4-week treatment was started. During the experiment, the hyperglycemia status of rats were evaluated with blood glucose measurement, oral glucose tolerance test, and insulin tolerance test; cognitive impairments were evaluated with the novel object recognition test, passive avoidance test and Morris' water maze test. Biochemical and histological analyzes of the relevant parameters were performed in serum and tissues obtained from rats. Results: Phlorizin and dapagliflozin improved diabetic and cognitive impairments, and biochemical analyzes supported these results. According to the histological analysis, pancreatic, hippocampus and cerebral cortex tissues showed improvement compared to the AD group, and immunohistochemical analyzes showed increased amyloid-b1-42 and and tau protein expression in the hippocampus and cerebral cortex in the AD group. Conclusion: According to the results obtained from this thesis study, non-selective SGLT inhibitor florizin and SGLT2 inhibitor dapagliflozin showed curative effects in T2DM-induced AD disease.